title: Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.
abstract: Celastrol is a triterpenoid compound extracted from the Chinese herb Tripterygium wilfordii Hook F. Previous research has revealed its anti-oxidant, anti-inflammatory, anti-cancer and immunosuppressive properties. Here, we investigated whether celastrol inhibits oxidized low-density lipoprotein (oxLDL) induced oxidative stress in RAW 264.7 cells. In addition, the effect of celastrol on atherosclerosis in vivo was assessed in apolipoprotein E knockout (apoE(-/-)) mouse fed a high-fat/high-cholesterol diet (HFC). We found that celastrol significantly attenuated oxLDL-induced excessive expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) and generation of reactive oxygen species (ROS) in cultured RAW264.7 macrophages. Celastrol also decreased IκB phosphorylation and degradation and reduced production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α and IL-6. Celastrol reduced atherosclerotic plaque size in apoE(-/-) mice. The expression of LOX-1 within the atherosclerotic lesions and generation of superoxide in mouse aorta were also significantly reduced by celastrol while the lipid profile was not improved. In conclusion, our results show that celastrol inhibits atherosclerotic plaque developing in apoE(-/-) mice via inhibiting LOX-1 and oxidative stress.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gu
authors.forename: Wenli
authors.initials: W
authors.lastname: Bai
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.forename: Yue
authors.initials: Y
authors.lastname: Gu
authors.forename: Guoliang
authors.initials: G
authors.lastname: Meng
authors.forename: Liping
authors.initials: L
authors.lastname: Xie
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Xiao
authors.forename: Liyang
authors.initials: L
authors.lastname: Shan
authors.forename: Suming
authors.initials: S
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Wei
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D050197:Atherosclerosis / Q000517:prevention & control*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D053978:Pentacyclic Triterpenes; D060888:Real-Time Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017931:DNA Primers; D016328:NF-kappa B; C495138:Olr1 protein, mouse; D053978:Pentacyclic Triterpenes; D051127:Scavenger Receptors, Class E; D014315:Triterpenes; C050414:celastrol